Effect of monoclonal anti-ANP antibodies on the acute functional adaptation to unilateral nephrectomy

The role of endogenous atrial natriuretic peptide (ANP) in the immediate response of sodium excretion to unilateral nephrectomy (UNX) was investigated in anesthetized euvolemic rats through measurement of UNX-induced change in plasma ANP concentration and the response of the remaining kidney to UNX following administration of monoclonal anti-ANP antibodies. The circulating ANP levels almost tripled (from 23 +/- 4 to 66 +/- 13 fmol/ml, P < 0.01) within two minutes after UNX, whereas no change resulted from sham intervention. In the control group receiving vehicle injection, UNX resulted in a twofold increase in urinary sodium excretion (from 1.39 +/- 0.25 to 2.88 +/- 0.28 mumol/min, P < 0.01) related to a decrease in the fractional reabsorption of sodium at both proximal and distal sites (estimated from fractional excretion of lithium). Urinary excretion of cyclic guanosine 3'-5'-monophosphate (cGMP) increased as well, but glomerular filtration rate did not change. In addition, UNX was associated with a short-lived (< 20 min) rise in systemic arterial pressure and a transient fall in right atrial pressure. Administration of monoclonal anti-ANP antibodies totally prevented the UNX-associated natriuresis by blunting both proximal and distal tubular reabsorption of sodium, and suppressed the rise in urinary cGMP excretion following UNX. The duration of the post-UNX increase in arterial pressure was longer when compared to values observed in controls. These observations indicate that ANP release is stimulated after uninephrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)